Cytomegalovirus (CMV) is a clinically relevant source of human congenital infections. Human CMV primary infection or reactivation of latent infections are also thought to play a major role in the mortality of organ transplant patients. Mouse cytomegalovirus (MCMV) infections are a convenient model for human CMV disease. This application takes MCMV infections one step further - into organ culture - in an attempt to further understand some of the basic cell biology and virology of CMV infections: 1. There is a known genetic resistance in vivo to the lethal effects of MCMV. I have evidence from tracheal organ culture that in addition to immunological factors, this resistance may also be based upon an innate cellular resistance to MCMV. I propose to extensively characterize this organ culture based resistance to MCMV. Parallel organ culture of MCMV resistant/susceptible mouse strains will be used with immunofluorescence and in situ hybridization assays to localize infected cells. Viral absorption and infection center assays will be peformed to see if receptors for the virus might be involved. Epithelial cell monolayers will also be infected with MCMV to gauge the importance of this cell type. Further genetic characterization of MCMV strain specificity will also be carried out. 2. Long term organ culture MCMV infections which have been obtained may be a useful model for chronic CMV infection. These persistent organ culture infections will be characterized by many of the methods described above. 3. Among the congenital defects which CMV can cause is deafness. Mouse inner ear organ cultures of 2 different types will be utilized in an attempt to establish a satisfactory model for this. Again, virus will be localized by immunofluorescence and in situ hybridization as well as by basic histological methods.